LATS2

Summary

LATS2 (large tumor suppressor kinase 2, HGNC:6515) is a protein-coding gene on chromosome 13q12.11, encoding Serine/threonine-protein kinase LATS2 (Q9NRM7). Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.

This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression.

Source: NCBI Gene 26524 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 170 total — 1 likely-pathogenic
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_014572

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6515
Approved symbol	LATS2
Name	large tumor suppressor kinase 2
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000150457
Ensembl biotype	protein_coding
OMIM	604861
Entrez	26524

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382592, ENST00000472754, ENST00000906119, ENST00000906120, ENST00000940303, ENST00000940304, ENST00000940305, ENST00000961821

RefSeq mRNA: 1 — MANE Select: NM_014572 NM_014572

CCDS: CCDS9294

Canonical transcript exons

ENST00000382592 — 8 exons

Exon	Start	End
ENSE00000995034	20983224	20983806
ENSE00000995036	20979691	20979797
ENSE00000995037	20981466	20981648
ENSE00001093489	20987881	20989304
ENSE00001492772	20973036	20975364
ENSE00001492905	21045685	21046230
ENSE00001926258	21061346	21061586
ENSE00003589665	20991272	20991404

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0580 / max 522.5211, expressed in 1764 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136381	33.0292	1764
136379	0.0165	7
136380	0.0123	3

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.77	gold quality
left ventricle myocardium	UBERON:0006566	98.50	gold quality
visceral pleura	UBERON:0002401	98.48	gold quality
parietal pleura	UBERON:0002400	98.36	gold quality
tibialis anterior	UBERON:0001385	98.18	gold quality
tibia	UBERON:0000979	98.01	gold quality
germinal epithelium of ovary	UBERON:0001304	97.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.68	gold quality
lower lobe of lung	UBERON:0008949	97.38	gold quality
amniotic fluid	UBERON:0000173	97.22	gold quality
saphenous vein	UBERON:0007318	97.14	gold quality
kidney epithelium	UBERON:0004819	97.07	gold quality
cauda epididymis	UBERON:0004360	96.92	gold quality
decidua	UBERON:0002450	96.56	gold quality
esophagus squamous epithelium	UBERON:0006920	95.75	gold quality
sperm	CL:0000019	95.73	gold quality
pericardium	UBERON:0002407	95.73	gold quality
vena cava	UBERON:0004087	95.72	gold quality
myocardium	UBERON:0002349	95.55	gold quality
renal medulla	UBERON:0000362	95.50	gold quality
layer of synovial tissue	UBERON:0007616	95.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.02	gold quality
deltoid	UBERON:0001476	94.95	gold quality
pancreatic ductal cell	CL:0002079	94.80	gold quality
endothelial cell	CL:0000115	94.73	gold quality
tendon of biceps brachii	UBERON:0008188	94.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.47	gold quality
secondary oocyte	CL:0000655	94.34	gold quality
synovial joint	UBERON:0002217	94.09	gold quality
cartilage tissue	UBERON:0002418	94.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
VEPH1	Repression

Upstream regulators (CollecTRI, top): AR, FOXP3, TP53, VEPH1, ZFP36

miRNA regulators (miRDB)

200 targeting LATS2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 40)

• of mammalian Lats2 and Lats1 control cell proliferation by negatively regulating different cell cycle check points. (PMID:12853976)
• LATS2 may play a role in androgen receptor-mediated transcription and contribute to the development of prostate cancer (PMID:15131260)
• S83 of Lats2 is a phosphorylation target of Aurora-A and this phosphorylation plays a role of the centrosomal localization of Lats2 (PMID:15147269)
• Lats2 induces apoptosis through downregulating anti-apoptotic proteins, BCL-2 and BCL-x(L), in human lung cancer cells. (PMID:15265683)
• Mst2, a STE20-family member and purported Hpo ortholog, phosphorylates and activates both Lats1 and Lats2 (PMID:15688006)
• Hypermethylation of the promoter region of LATS2 likely plays an important role in the down-regulation of LATS2 mRNA level in breast cancers, and breast cancers with a decreased expression of LATS2 mRNA level have a biologically aggressive phenotype. (PMID:15746036)
• LATS1 and LATS2 mRNA was down-regulated in astrocytoma by hypermethylation of the promoter (PMID:17049657)
• Kpm/Lats2 is involved in the fate of p73 through the phosphorylation of YAP2 by Kpm/Lats2 and the induction of p73 target genes that underlie chemosensitivity of leukemic cells. (PMID:18565851)
• Lats2 affects both growth and death of cardiac myocytes, but it primarily regulates the size of the heart and acts as an endogenous negative regulator of cardiac hypertrophy. (PMID:18927464)
• tumor-specific mutations and down-regulation of the gene expression is observed in non-small cell lung carcinoma patients (PMID:19008013)
• Data show that LATS2 protein expression is mediated by miR-373 at the post-transcriptional level and inversely correlates with miR-373 amounts in esophageal cancer cell lines. (PMID:19501585)
• collection of genes identified suggests that LATS1/2 function through diverse mechanisms and multiple signaling pathways including the Hippo signaling pathway, as well as the p53, Ras-ERK, or WNT networks, to inhibit tumor progression (PMID:19799973)
• Lats2 might have an important role in quenching H-Ras-induced transformation. (PMID:19855428)
• down-regulation of expression in gastric cancer cell is associated with oncogenesis (PMID:19937137)
• LATS2 tumor suppressor gene is regulated by tristetraprolin (PMID:20335167)
• LATS2 is de-methylated and overexpressed in nasopharyngeal carcinoma and predicts poor prognosis (PMID:20932276)
• Data show that Lats2 and ASPP1 shunt p53 to proapoptotic promoters and promote the death of polyploid cells. (PMID:21041410)
• In response to ultraviolet radiation, Lats2 is phosphorylated by Chk1 and Chk2 at S408. (PMID:21118956)
• KIBRA associates with and activates Lats (large tumor suppressor) 1 and 2 kinases by stimulating their phosphorylation on the hydrophobic motif (PMID:21233212)
• Inactivation of LATS2 is one of the key mechanisms for constitutive activation of YAP, which induces deregulation of MM cell proliferation. (PMID:21245096)
• Data suggest that defective expression of LATS2 is attributable to FOXP3 defects and may be a major independent determinant of YAP protein elevation in cancer. (PMID:21278236)
• Results reveal a functional connection between the pRB and Hippo tumor suppressor pathways, and suggest that low levels of LATS2 may undermine the ability of pRB to induce a permanent cell cycle arrest in tumor cells. (PMID:21498571)
• the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2. (PMID:21822051)
• AMOTL2 is as a novel activator of LATS2. (PMID:21832154)
• Lats2 kinase as a novel regulator of Snail1 protein level, subcellular localization, and thus, activity (PMID:21952048)
• MicroRNA-31 regulated by the extracellular regulated kinase is involved in vascular smooth muscle cell growth via large tumor suppressor homolog (PMID:22020941)
• Yap induction mediated by inactivation of Lats is observed in hepatic malignancies. (PMID:22098159)
• LATS2 represses reprogramming in cells by post-transcriptionally antagonizing TAZ but not YAP, two downstream effectors of the Hippo pathway. (PMID:22286172)
• LATS2 played important roles in mediating miR-93 functions associated with angiogenesis and metastasis by silencing. (PMID:23111389)
• Identifying novel kinases which modulate Estrogen Receptor alpha activity is relevant to therapeutics. LATS2 modulates Estrogen Receptor alpha-regulated gene transcription, through direct and/or indirect interactions with Estrogen Receptor alpha. (PMID:23267128)
• At low cell density, overexpression of the Hippo pathway kinase large tumor suppressor 2 (Lats2) inhibited c-Abl activity. (PMID:23852372)
• Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis. Findings describe a novel Lats2-dependent mechanism for induction of cell death in response to severe DNA damage. (PMID:23886938)
• LATS1 and LATS2 mutations from cancers can lead to loss or reduction of their growth-inhibitory activity (PMID:24026096)
• Data indicate that the phosphorylation of Amot130 by LATS1/2 is found to be a key feature that enables it to inhibit Yes-associated protein (YAP) dependent signaling and cell growth. (PMID:24101513)
• Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis. (PMID:24106267)
• These results collectively suggest that the Hippo pathway negatively regulates the actin-binding activity of Amot family members through direct phosphorylation. (PMID:24225952)
• LATS2 directly interacts with beta-catenin and disrupts beta-catenin iteraction with BCL9. (PMID:24360964)
• these results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. (PMID:24735543)
• LATS2 over-expression is associated with acute myeloid leukemia. (PMID:24743869)
• MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3’-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus (PMID:24779718)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	lats2	ENSDARG00000078864
mus_musculus	Lats2	ENSMUSG00000021959
rattus_norvegicus	Lats2	ENSRNOG00000056343
drosophila_melanogaster	CG32944	FBGN0052944
drosophila_melanogaster	dop	FBGN0267390
caenorhabditis_elegans		WBGENE00002192
caenorhabditis_elegans	wts-1	WBGENE00007047
caenorhabditis_elegans		WBGENE00010838
caenorhabditis_elegans		WBGENE00011992

Paralogs (13): MAST4 (ENSG00000069020), MAST2 (ENSG00000086015), MAST3 (ENSG00000099308), SGK2 (ENSG00000101049), SGK3 (ENSG00000104205), DMPK (ENSG00000104936), MAST1 (ENSG00000105613), SGK1 (ENSG00000118515), MASTL (ENSG00000120539), LATS1 (ENSG00000131023), STK32B (ENSG00000152953), STK32C (ENSG00000165752), STK32A (ENSG00000169302)

Protein

Protein identifiers

Serine/threonine-protein kinase LATS2 — Q9NRM7 (reviewed: Q9NRM7)

Alternative names: Kinase phosphorylated during mitosis protein, Large tumor suppressor homolog 2, Serine/threonine-protein kinase kpm, Warts-like kinase

All UniProt accessions (1): Q9NRM7

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ. Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of ‘Ser-265’ of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7.

Subunit / interactions. Interacts with and is phosphorylated by AURKA. Binds to AR. Interacts with AJUBA during mitosis and this complex regulates organization of the spindle apparatus through recruitment of gamma-tubulin to the centrosome. Interacts (via PPxY motif) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP and AJUBA. Interacts with SNAI1. Interacts with WWC1, WWC2 and WWC3 (via their WW domains). Interacts (via UBA domain) with ubiquitinated AMOTL2; the interaction promotes LATS2 phosphorylation of YAP1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Nucleus.

Tissue specificity. Expressed at high levels in heart and skeletal muscle and at lower levels in all other tissues examined.

Post-translational modifications. Autophosphorylated and phosphorylated during M-phase and the G1/S-phase of the cell cycle. Phosphorylated and activated by STK3/MST2. Phosphorylated by MAP4Ks; in parallel to STK3/MST2 and resulting to its activation. Phosphorylation by NUAK2 may regulate its activity in phosphorylation and inactivation YAP1.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

RefSeq proteins (1): NP_055387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR009060	UBA-like_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR050236	Ser_Thr_kinase_AGC	Family

Pfam: PF00069, PF00433

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (43 total): region of interest 8, sequence variant 7, compositionally biased region 5, modified residue 5, mutagenesis site 4, sequence conflict 4, domain 3, binding site 2, helix 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4ZRI	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRM7-F1	56.73	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 791 (proton acceptor)

Ligand- & substrate-binding residues (2): 674–682; 697

Post-translational modifications (5): 83, 279, 380, 576, 1041

Mutagenesis-validated functional residues (4):

Position	Phenotype
83	fails to localize at the centromere during interphase.
697	loss of kinase activity, autophosphorylation and tumor suppressor activity.
872	loss of tumor suppressor activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2028269	Signaling by Hippo
R-HSA-162582	Signal Transduction

MSigDB gene sets: 378 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_HIPPO_SIGNALING, GOBP_BLASTOCYST_FORMATION

GO Biological Process (21): G1/S transition of mitotic cell cycle (GO:0000082), inner cell mass cell fate commitment (GO:0001827), inner cell mass cellular morphogenesis (GO:0001828), protein phosphorylation (GO:0006468), intracellular protein localization (GO:0008104), hormone-mediated signaling pathway (GO:0009755), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), keratinocyte differentiation (GO:0030216), hippo signaling (GO:0035329), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), negative regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045736), regulation of organ growth (GO:0046620), cell division (GO:0051301), canonical Wnt signaling pathway (GO:0060070), negative regulation of cell growth involved in contact inhibition (GO:0060243), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of protein localization to nucleus (GO:1900181), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), positive regulation of hippo signaling (GO:0035332), mitotic cell cycle phase transition (GO:0044772)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), centriolar satellite (GO:0034451), centrosome (GO:0005813), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
inner cell mass cell differentiation	2
signal transduction	2
intracellular anatomical structure	2
protein kinase activity	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cell fate commitment	1
cell morphogenesis	1
embryonic morphogenesis	1
phosphorylation	1
protein modification process	1
macromolecule localization	1
cellular response to hormone stimulus	1
transforming growth factor beta receptor signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to transforming growth factor beta stimulus	1
epidermal cell differentiation	1
skin development	1
intracellular signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase activity	1
negative regulation of cell cycle	1
negative regulation of protein serine/threonine kinase activity	1
negative regulation of cyclin-dependent protein kinase activity	1
organ growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
cellular process	1
Wnt signaling pathway	1
negative regulation of cell growth	1
contact inhibition	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
protein localization to nucleus	1

Protein interactions and networks

STRING

1514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LATS2	SAV1	Q9H4B6	979
LATS2	MDM2	Q00987	953
LATS2	MOB1B	Q7L9L4	918
LATS2	SIAH2	O43255	915
LATS2	MOB1A	Q9H8S9	914
LATS2	NF2	P35240	834
LATS2	YAP1	P46937	828
LATS2	WWC1	Q8IX03	814
LATS2	RBL2	Q08999	776
LATS2	DGCR8	Q8WYQ5	746
LATS2	TEAD1	P28347	711
LATS2	WWTR1	Q9GZV5	710
LATS2	TP53	P04637	695
LATS2	CDKN1A	P38936	656
LATS2	AMOTL2	Q9Y2J4	651

IntAct

69 interactions, top by confidence:

A	B	Type	Score
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
LATS2	MOB1B	psi-mi:“MI:0915”(physical association)	0.830
LATS2	MOB1A	psi-mi:“MI:0915”(physical association)	0.740
MOB1A	LATS2	psi-mi:“MI:0915”(physical association)	0.740
LATS2	MOB1A	psi-mi:“MI:0914”(association)	0.740
AJUBA	LATS2	psi-mi:“MI:0915”(physical association)	0.710
LATS2	AJUBA	psi-mi:“MI:0915”(physical association)	0.710
LATS1	YWHAH	psi-mi:“MI:0914”(association)	0.670
SIAH2	LATS2	psi-mi:“MI:0915”(physical association)	0.630
LATS2	SIAH2	psi-mi:“MI:0915”(physical association)	0.630
SIAH2	LATS2	psi-mi:“MI:0407”(direct interaction)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
DCAF1	LATS2	psi-mi:“MI:0915”(physical association)	0.540
YAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LATS2		psi-mi:“MI:0915”(physical association)	0.520
SNAI1	LATS2	psi-mi:“MI:0915”(physical association)	0.500
LATS2	SNAI1	psi-mi:“MI:0403”(colocalization)	0.500
FHL3	LATS2	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (480): CTNNB1 (Affinity Capture-Western), LATS2 (Affinity Capture-Western), LATS2 (Reconstituted Complex), CDKN1A (Biochemical Activity), LATS2 (Biochemical Activity), LATS2 (Affinity Capture-Western), LATS2 (Co-crystal Structure), LIMD1 (Affinity Capture-Western), AJUBA (Affinity Capture-Western), WTIP (Affinity Capture-Western), LATS2 (Affinity Capture-Western), LATS2 (Affinity Capture-Western), LATS2 (Affinity Capture-Western), LATS2 (Affinity Capture-Western), LATS2 (Proximity Label-MS)

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

Diamond homologs: A2VDV2, A8WVU9, A8XJL7, E9PSL7, F4HPN2, F4HYG2, F4J6F6, M3TYT0, O01583, O13310, O14578, O15021, O45797, O54874, O60307, O75116, O77819, O94487, O95835, P00517, P05131, P05383, P0C1B1, P12688, P17612, P18961, P22204, P22694, P25321, P27791, P31034, P32328, P36887, P38679, P38938, P49025, P53894, P54265, P54644, P68180

SIGNOR signaling

44 interactions.

A	Effect	B	Mechanism
AURKA	up-regulates	LATS2	phosphorylation
MOB1A	up-regulates	LATS2	binding
MOB1B	up-regulates	LATS2	binding
LATS2	up-regulates	YWHAG	phosphorylation
LATS2	down-regulates	WWTR1	phosphorylation
STK3	up-regulates	LATS2	phosphorylation
STK4	up-regulates	LATS2	phosphorylation
LATS2	up-regulates	SNAI1	phosphorylation
LATS2	“down-regulates quantity by repression”	VEPH1	“transcriptional regulation”
VEPH1	“down-regulates quantity by repression”	LATS2	“transcriptional regulation”
F2R	down-regulates	LATS2
F-actin_assembly	down-regulates	LATS2
LATS2	down-regulates	YAP1	phosphorylation
“sphingosine 1-phosphate”	down-regulates	LATS2
(R)-adrenaline	up-regulates	LATS2
GCG	up-regulates	LATS2
NF2	up-regulates	LATS2	binding
LATS2	“down-regulates quantity by destabilization”	YAP1	phosphorylation
Mob1	up-regulates	LATS2	binding
STK3/4	up-regulates	LATS2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by Hippo	5	93.8×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	5	111.0×	5e-07
intracellular protein localization	5	15.9×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — LUSC, PAST, PLMESO.

Clinical variants and AI predictions

ClinVar

170 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	136
Likely benign	13
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
619198	NM_014572.3(LATS2):c.2699_2700insC (p.Val901fs)	Likely pathogenic

SpliceAI

2042 predictions. Top by Δscore:

Variant	Effect	Δscore
13:20975363:AC:A	acceptor_gain	1.0000
13:20975363:ACC:A	acceptor_loss	1.0000
13:20975364:CC:C	acceptor_gain	1.0000
13:20983802:CCAGC:C	acceptor_gain	1.0000
13:20983803:CAGC:C	acceptor_gain	1.0000
13:20983803:CAGCC:C	acceptor_gain	1.0000
13:20983804:AGC:A	acceptor_gain	1.0000
13:20983804:AGCCT:A	acceptor_loss	1.0000
13:20983805:GC:G	acceptor_gain	1.0000
13:20983805:GCC:G	acceptor_loss	1.0000
13:20983806:CC:C	acceptor_gain	1.0000
13:20983807:C:CC	acceptor_gain	1.0000
13:20983807:C:CG	acceptor_loss	1.0000
13:20983808:T:G	acceptor_loss	1.0000
13:20983809:G:C	acceptor_gain	1.0000
13:20983809:G:GC	acceptor_gain	1.0000
13:20983811:G:C	acceptor_gain	1.0000
13:20983811:G:GC	acceptor_gain	1.0000
13:20989300:CTTTC:C	acceptor_gain	1.0000
13:20989301:TTTC:T	acceptor_gain	1.0000
13:20989302:TTC:T	acceptor_gain	1.0000
13:20989302:TTCC:T	acceptor_loss	1.0000
13:20989303:TC:T	acceptor_gain	1.0000
13:20989304:CC:C	acceptor_gain	1.0000
13:20989304:CCTG:C	acceptor_loss	1.0000
13:20989306:T:A	acceptor_loss	1.0000
13:20991266:GCTCA:G	donor_loss	1.0000
13:20991267:CTCAC:C	donor_loss	1.0000
13:20991270:A:C	donor_loss	1.0000
13:20991287:TAATG:T	donor_gain	1.0000

AlphaMissense

7143 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:20975002:G:C	F1045L	1.000
13:20975002:G:T	F1045L	1.000
13:20975004:A:G	F1045L	1.000
13:20975006:C:A	R1044M	1.000
13:20975009:C:G	R1043P	1.000
13:20975011:G:C	F1042L	1.000
13:20975011:G:T	F1042L	1.000
13:20975013:A:G	F1042L	1.000
13:20975017:G:C	F1040L	1.000
13:20975017:G:T	F1040L	1.000
13:20975018:A:G	F1040S	1.000
13:20975019:A:G	F1040L	1.000
13:20975131:G:C	F1002L	1.000
13:20975131:G:T	F1002L	1.000
13:20975133:A:G	F1002L	1.000
13:20979769:A:C	S898R	1.000
13:20979769:A:T	S898R	1.000
13:20979771:T:G	S898R	1.000
13:20979774:A:G	W897R	1.000
13:20979774:A:T	W897R	1.000
13:20979779:T:A	D895V	1.000
13:20979779:T:G	D895A	1.000
13:20979780:C:G	D895H	1.000
13:20979781:A:C	C894W	1.000
13:20979782:C:T	C894Y	1.000
13:20981497:G:C	N878K	1.000
13:20981497:G:T	N878K	1.000
13:20981507:C:T	G875E	1.000
13:20981508:C:A	G875W	1.000
13:20981508:C:G	G875R	1.000

dbSNP variants (sampled 300 via entrez): RS1000048775 (13:21011954 A>G), RS1000062999 (13:20986812 T>A,C), RS1000088880 (13:21034167 C>T), RS1000137005 (13:21024107 A>G), RS1000151682 (13:20993831 T>C), RS1000177092 (13:21060787 T>C), RS1000200236 (13:20998431 G>A,C), RS1000203117 (13:21033825 C>A), RS1000246967 (13:20986911 G>A), RS1000263774 (13:21014593 G>T), RS1000290558 (13:20974999 A>G), RS1000295308 (13:21054651 T>C), RS1000304118 (13:21062459 G>A,T), RS1000341723 (13:20980704 T>C,G), RS1000445070 (13:21045513 C>T)

Disease associations

OMIM: gene MIM:604861 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): malignant peritoneal mesothelioma (MONDO:0005512)

Orphanet (1): Malignant peritoneal mesothelioma (Orphanet:168811)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007672_6	3-month functional outcome in ischaemic stroke (modified Rankin score)	6.000000e-06
GCST010002_180	Refractive error	1.000000e-11
GCST012227_480	Hip circumference adjusted for BMI	6.000000e-09
GCST012490_287	Femur bone mineral density x serum urate levels interaction	4.000000e-09
GCST012490_34	Femur bone mineral density x serum urate levels interaction	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523992 (PROTEIN FAMILY), CHEMBL5907 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 116,140 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL5089410	PILAVAPADIN	2	55
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622
CHEMBL494089	GSK-690693	1	2,061
CHEMBL574738	AST-487	1	451

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs558614	LATS2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NDR family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
TRULI	Inhibition	9.7	pIC50
lestaurtinib	Inhibition	9.0	pKd
staurosporine	Inhibition	7.77	pKd
Lpi-1	Binding	6.94	pKd
GSK690693	Inhibition	6.85	pKd
sunitinib	Inhibition	6.34	pKd
A-674563	Inhibition	6.21	pKd
midostaurin	Inhibition	5.66	pKd
AST-487	Inhibition	5.52	pKd

ChEMBL bioactivities

356 potent at pChembl≥5 of 421 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.28	IC50	0.52	nM	CHEMBL6082870
9.00	IC50	1	nM	CHEMBL4592699
9.00	Kd	1	nM	LESTAURTINIB
8.70	IC50	2	nM	CHEMBL4572019
8.70	IC50	2	nM	CHEMBL4577857
8.43	IC50	3.76	nM	STAUROSPORINE
8.40	IC50	4	nM	CHEMBL4551441
8.40	IC50	4	nM	CHEMBL4585067
8.40	IC50	4	nM	CHEMBL4454440
8.38	IC50	4.17	nM	STAUROSPORINE
8.22	IC50	6	nM	CHEMBL4439529
8.22	IC50	6	nM	CHEMBL5303533
8.10	IC50	8	nM	CHEMBL4464251
8.10	IC50	8	nM	CHEMBL4522021
8.06	IC50	8.62	nM	STAUROSPORINE
7.96	IC50	11	nM	CHEMBL4532021
7.92	IC50	12	nM	CHEMBL4436873
7.82	IC50	15	nM	CHEMBL4574721
7.82	IC50	15	nM	CHEMBL4565580
7.77	Kd	17	nM	STAUROSPORINE
7.75	IC50	18	nM	CHEMBL4476180
7.75	Kd	18	nM	CHEMBL5434183
7.72	IC50	19	nM	CHEMBL4472285
7.72	IC50	19	nM	CHEMBL4551441
7.70	IC50	20	nM	CHEMBL4513243
7.68	IC50	21	nM	CHEMBL4533967
7.62	IC50	24	nM	CHEMBL6175274
7.58	IC50	26	nM	CHEMBL4566869
7.52	IC50	30	nM	CHEMBL4547445
7.52	IC50	30	nM	CHEMBL4529548
7.47	IC50	34	nM	CHEMBL4449036
7.42	Kd	38	nM	CHEMBL5414359
7.40	IC50	40	nM	CHEMBL4577857
7.30	IC50	50	nM	CHEMBL4472817
7.30	IC50	50	nM	CHEMBL4534258
7.26	Kd	55	nM	ERKi
7.20	IC50	63	nM	CHEMBL4517252
7.17	IC50	67	nM	CHEMBL4531857
7.16	IC50	70	nM	CHEMBL5433617
6.95	IC50	113	nM	CHEMBL4443335
6.88	IC50	131	nM	CHEMBL4472306
6.87	Kd	135	nM	CHEMBL4465866
6.85	IC50	141	nM	CHEMBL4518582
6.85	Kd	140	nM	GSK-690693
6.78	IC50	165	nM	CHEMBL4471995
6.77	IC50	170	nM	CHEMBL4571192
6.73	IC50	185	nM	CHEMBL4571192
6.73	IC50	187	nM	CHEMBL4573735
6.70	IC50	198	nM	CHEMBL4470612
6.70	IC50	202	nM	CHEMBL4454440

PubChem BioAssay actives

44 with measured affinity, of 226 total; 30 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507586: Binding affinity to LATS2	kd	0.0010	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531744: Inhibition of human LATS2 using KKRNRRLSVA as substrate by [gamma-33P]-ATP assay	ic50	0.0038	uM
5-[(5S)-5-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-3-methyl-2H-indazole	2030654: Binding affinity to LATS2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.0180	uM
5-[4-[(4-chlorophenyl)methyl]-5-methyl-1,2,4-triazol-3-yl]-3-methyl-2H-indazole	2030654: Binding affinity to LATS2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.0380	uM
6-(3-methylimidazol-4-yl)-4-(7H-purin-6-yl)-2,3-dihydro-1,4-thiazine	2019965: Inhibition of LATS2 (unknown origin)	ic50	0.0700	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526178: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged LATS2 (unknown origin) (553 to 1088 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1350	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625083: Binding constant for LATS2 kinase domain	kd	0.1400	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526178: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged LATS2 (unknown origin) (553 to 1088 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.2230	uM
3-methyl-5-[5-methyl-4-[[4-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-3-yl]-2H-indazole	2030654: Binding affinity to LATS2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.2500	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625083: Binding constant for LATS2 kinase domain	kd	0.3800	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	436021: Binding constant for LATS2 kinase domain	kd	0.4300	uM
5-[(5S)-5-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-3-methyl-2H-pyrazolo[4,3-b]pyridine	2030654: Binding affinity to LATS2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.4600	uM
Sunitinib	436021: Binding constant for LATS2 kinase domain	kd	0.4600	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	436021: Binding constant for LATS2 kinase domain	kd	0.5300	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625083: Binding constant for LATS2 kinase domain	kd	0.6200	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	436021: Binding constant for LATS2 kinase domain	kd	0.6400	uM
(2S)-1-[[2-(difluoromethyl)-6-[2-(difluoromethyl)-4-pyridinyl]-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	1826908: Inhibition of LATS2 (unknown origin)	ic50	0.6600	uM
5-[(5S)-5-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-3-methyl-2H-pyrazolo[3,4-b]pyridine	2030654: Binding affinity to LATS2 (unknown origin) assessed as dissociation constant by competitive binding assay	kd	0.7300	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625083: Binding constant for LATS2 kinase domain	kd	1.5000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	436021: Binding constant for LATS2 kinase domain	kd	1.7000	uM
4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenol	436021: Binding constant for LATS2 kinase domain	kd	1.7000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625083: Binding constant for LATS2 kinase domain	kd	1.8000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625083: Binding constant for LATS2 kinase domain	kd	2.0000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625083: Binding constant for LATS2 kinase domain	kd	2.1000	uM
Midostaurin	436021: Binding constant for LATS2 kinase domain	kd	2.2000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	436021: Binding constant for LATS2 kinase domain	kd	3.0000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625083: Binding constant for LATS2 kinase domain	kd	4.0000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625083: Binding constant for LATS2 kinase domain	kd	4.0000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625083: Binding constant for LATS2 kinase domain	kd	6.5000	uM
Fedratinib	625083: Binding constant for LATS2 kinase domain	kd	8.0000	uM

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	decreases expression, increases expression, affects binding	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	affects binding, decreases reaction, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases expression, affects expression	2
Zinc	affects binding, decreases reaction, affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	increases expression	2
methylmercuric chloride	increases expression	1
bisphenol A	affects expression	1
arsenite	affects binding, decreases reaction	1
fisetin	increases phosphorylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
ginsenoside Rg3	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	increases expression, affects binding	1

ChEMBL screening assays

170 unique, capped per target: 170 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4420664	Binding	Inhibition of LATS in human HaCaT cells assessed as reduction in YAP phosphorylation level incubated for 2 hrs by HTRF assay	6-6 Fused Bicyclic Heteroaryl Compounds and their Use as LATS Inhibitors

Cellosaurus cell lines

18 cell lines: 17 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1430	MSTO-211H	Cancer cell line	Male
CVCL_1518	NCI-H2052	Cancer cell line	Male
CVCL_5179	Y-MESO-14	Cancer cell line	Male
CVCL_5180	Y-MESO-21	Cancer cell line	Male
CVCL_5183	Y-MESO-26B	Cancer cell line	Male
CVCL_5184	Y-MESO-27	Cancer cell line	Male
CVCL_5187	Y-MESO-30	Cancer cell line	Male
CVCL_B8JL	Abcam HCT 116 LATS2 KO	Cancer cell line	Male
CVCL_B8Y9	Abcam MCF-7 LATS2 KO	Cancer cell line	Female
CVCL_B9LV	Abcam A-549 LATS2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01592383	PHASE2	COMPLETED	Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma
NCT06057935	PHASE2	RECRUITING	A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma
NCT06543069	PHASE2	RECRUITING	Sintilimab, Bevacizumab, Pemetrexed, and Cisplatin for Unresectable MPeM
NCT06756035	PHASE1	RECRUITING	CT-95 in Advanced Cancers Associated With Mesothelin Expression
NCT02151448	PHASE1/PHASE2	COMPLETED	αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies
NCT02535312	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin